4.6 Article

Microfluidic chip interfacing microdialysis and mass spectrometry for in vivo monitoring of nanomedicine pharmacokinetics in real time

Journal

JOURNAL OF CHROMATOGRAPHY A
Volume 1683, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.chroma.2022.463520

Keywords

Microfluidics; Pharmacokinetics; Liposome doxorubicin; Microdialysis; Mass spectrometry

Funding

  1. Canada Research Chairs program, New Frontiers in Research Fund-Exploration [NFRFE-2018-01005]
  2. Scientific and Technological Foundation of Shenzhen, China [GJHZ20180928161212140]
  3. Sanming Project of Medicine in Shenzhen [SZSM201612097]
  4. Shenzhen Key Medical Discipline Construction Fund [SZXK075]
  5. NSERC Discovery Grants Program [RGPIN-2016-05569, RGPIN-2015-03793]
  6. Cape Breton University RISE program
  7. Post-doctoral Foundation Project of Shenzhen Polytechnic [6019330007K]

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Although liposomes have shown significant success in clinical drug delivery, studying the pharmacokinetics of liposomal nanomedicines remains challenging due to the difficulty in accurately measuring low concentrations of free drug. This study presents a microdialysis-based microfluidic chip interfaced with mass spectrometry to address this issue. By incorporating an effective anti-foulant, PEG 20,0 0 0, the microfluidic chip demonstrated excellent drug extraction and desalting efficiency, providing a promising approach for real-time monitoring of nanomedicine pharmacokinetic profiles.
Although liposomes have demonstrated significant clinical success as drug delivery vehicles, pharmacoki-netic (PK) profiling of liposomal nanomedicines remains difficult due to technical challenges accurately measuring low concentrations of free drug in complex biological matrices. Microdialysis (MD) is well es-tablished as a powerful in vivo sampling tool for PK studies, but non-volatile salts present in the micro-dialysate are incompatible with mass spectrometry (MS) analysis without tedious sample pre-treatment. To address this issue, a mu SPE-based microfluidic chip was fabricated to interface MD with MS. By incorpo-rating PEG 20,0 0 0 as an effective anti-foulant, the mu SPE-based microfluidic chip demonstrated excellent efficiencies in drug extraction and de-salting of the microdialysate, providing a promising approach to real-time monitoring of nanomedicine PK profiles.(c) 2022 Elsevier B.V. All rights reserved.

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